The conditions and factors influencing male fertility are not well understood at present. Epidemiological studies of human infertility have long suggested an association between this disorder and genital mycoplasma infection. This association can now be investigated in detail due to recent advances in our own and other laboratories indicating that these organisms actually adhere to human and animal spermatozoa and that Mycoplasma and Ureaplasma can now be detected, cultured and preserved in the laboratory. Protein carboxy methylase and its substrate methyl acceptor protein are known to be important in the motility of bacteria and leukocytes. We have obtained evidence suggesting that this enzyme system is also involved in the control of spermatozoal motility and that asthenozoospermia in man is related to abnormalities of methylation. The objectives of the studies proposed here are to determine the effects of these two factors on spermatozoal function. Specifically, we will study the effect of mycoplasmas on sperm motility, transport through the female genital tract and fertilizing ability. The effect of mycoplasma will be studied longitudinally to determine the stability of mycoplasma colonization and which of these sperm function tests is the most reliable predictor of mycoplasma-induced infertility. The reversibility of these effects will then be studied in infertile patients after appropriate therapy. In addition we will investigate the extent to which abnormal methylation is associated with various disorders of sperm motility. The results of these studies will provide us with more meaningful methods for the diagnosis of male fertility disorders and new approaches to the treatment of human infertility.